The resolution of enantiomers by enantioselective hydrolysis with an enzyme is known. However, the recent discovery that many hydrolytic enzymes work well in low polarity organic solvents (Cambou, B. and Kilbanov, A. M. J. Am. Chem. Soc., 1984, 106, 2687; Zaks, A., and Kilbanov, A. M., Science, 1984, 224, 1249) has allowed for enzymatic resolution to be extended to new reactions such as esterification (Cambou, B. and Kilbanov, A. M., Biotechnology and Bioengineering, 1984, XXVI, 1449), and transesterification (Cambou, B. and Kilbanov, A. M., J. Am. Chem. Soc., 1984, 106, 2687; Cambou, B. and Kilbanov, A. M., Biotechnology and Bioengineering, 1984, XXVI, 1449).
Resolution by enzymatic transesterification solves some of the problems associated with enzymatic hydrolyses. Among these are the low solubility of many organic compounds in water, the difficulty of recovering the enzyme for reuse, and the requirement for adjusting the ph as the reaction progresses. Moreover, an increase in enzyme stability has been reported when it is used in an organic solvent and higher reaction temperatures are tolerated (Zaks, A. and Kilbanov, A. M., Science, 1984, 224, 1249).
The resolution of a racemic mixture of esters may be carried out by transesterifying one enantiomer of a racemic ester with an achiral alcohol (Cambou, B. and Kilbanov, A. M. Biotechnology and Bioengineering, 1984, XXVI, 1449). More commonly, however, one enantiomer of a racemic alcohol transesterifiers and achiral ester. (Cambou, B. and Kilbanov, A. M., J. Am. Chem. Soc., 1984, 106, 2687; Cambou, B. and Kilbanov, A. M., Biotechnology and Bioengineering, 1984, XXVI, 1449). The latter case, which is useful for resolving alcohols, leads to the necessity for separating an ester from an alcohol. The first case, which is useful for resolving racemic mixtures of esters, leaves both enantiomers in the form of esters. The separation of the isomers in most cases requires tedious chromatography or careful distillation. (Cambou, B. and Klibanov, A. M., Biotechnology and Bioengineering, 1984, XXVI, 1449). This has been a substantial drawback which accounts for the limited application of this technology up to the present time.
The resolution of 3,4'-epoxybutyrate by stereoselective enzymatic hydrolysis of its methyl or other alkyl esters was recently reported by Mohr et al. (Mohr et al., Helv. Chim. Acta., 1987, 70, 142; Mohr et al., Tetrahedron Letters, 1989, 30 (19(, 2513) and by Bianchi et al. (Bianchi et al., J. Org. Chem., 1988, 53, 104)). Mohr et al. hydrolyzed a methyl ester with pig liver esterase and obtained the unchanged (R) ester and the (S) acid. However, the enantiomeric excesses of each compound after separation was not very high. Bianchi et al., supra, conducted the reaction with 13 different enzymes and concluded that porcine pancreatic lipase (PPL) provides the best stereoselectivity when alkyl, e.g., butyl, isobutyl and octyl, esters are hydrolyzed.